Prevailing Hypothesis For Schizophrenia Essay

Assignment must be typed and a minimum of 10 pages, 5 evidence-based references are required and cited accordingly. The prevailing hypothesis for schizophrenia implicates the neurotransmitter dopamine as playing a key role in the development of the disease. Dopamine acts on several areas of the brain with differing effects. Please outline the key dopamine pathways and the implications of antipsychotic use on each pathway.Prevailing Hypothesis For Schizophrenia Essay

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The treatment of schizophrenia has evolved over the past half century primarily in the context of antipsychotic drug development. Although there has been significant progress resulting in the availability and use of numerous medications, these reflect three basic classes of medications (conventional (typical), atypical and dopamine partial agonist antipsychotics) all of which, despite working by varying mechanisms of actions, act principally on dopamine systems. Many of the second-generation (atypical and dopamine partial agonist) antipsychotics are believed to offer advantages over first-generation agents in the treatment for schizophrenia. However, the pharmacological properties that confer the different therapeutic effects of the new generation of antipsychotic drugs have remained elusive, and certain side effects can still impact patient health and quality of life. Moreover, the efficacy of antipsychotic drugs is limited prompting the clinical use of adjunctive pharmacy to augment the effects of treatment. In addition, the search for novel and nondopaminergic antipsychotic drugs has not been successful to date, though numerous development strategies continue to be pursued, guided by various pathophysiologic hypotheses. This article provides a brief review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotics, and focuses on novel targets for therapeutic agents for future drug development.Prevailing Hypothesis For Schizophrenia Essay

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The therapeutic armamentarium for the treatment of schizophrenia has grown and diversified in the half century since the advent of chlorpromazine and the beginning of the pharmacologic era in psychiatry. Over the past decade, much of our attention regarding the treatment for schizophrenia and related psychotic disorders has focused on a new class of antipsychotic medications. The reintroduction of clozapine represented a major step forward, and led to the proliferation of ‘atypical’ or second-generation antipsychotics (SGAs), including risperidone, olanzapine, quetiapine, ziprasidone, sertindole and zotepine. In fact, there is growing evidence that most of the new medications can offer some advantages over ‘typical’ or first-generation antipsychotics (FGAs) such as greater improvement in negative symptoms, cognitive impairment, relapse prevention, functional capacity, and quality of life with fewer extrapyramidal symptoms (EPS), and less tardive dyskinesia (TD) (for a review, see Miyamoto et al1). Accordingly, many clinicians are prescribing these new antipsychotics as first-line agents for acute and maintenance therapy for schizophrenia.2, 3, 4, 5 However, these advantages, thus far, have been regarded as incremental and not necessarily substantial. Prevailing Hypothesis For Schizophrenia Essay In addition, concerns about side effects such as EPS have been replaced by other distressing side effects, including weight gain, hyperglycemia and dyslipidemia. At present, we are still in the process of defining fully the clinical profiles of new agents in terms of the extent of their therapeutic efficacy and adverse effects, on a variety of other outcomes including cognition, affect, suicide, subjective response, social and vocational function, cost effectiveness, etc.6

Although intensive research on the new antipsychotic drugs has led to a greater understanding of the biochemical effects of these drugs, the pharmacological mechanisms underlying their various therapeutic properties remain to be identified. Moreover, an agent like clozapine that was clinically superior to other highly selective dopamine D2 antagonists demanded reconsideration of the principal mechanisms of action of antipsychotics as well as the pathophysiological mechanisms in schizophrenia.6, 7 In addition, the limitations of existing antipsychotic drugs to alleviate all of the pathologic dimensions of the illness (ie negative symptoms, cognitive deficits and social disabilities) have produced an awareness that no single treatment may be sufficient and prompted the search for compounds that can be used adjunctively with antipsychotic drugs. Various adjunctive treatments, including benzodiazepines, lithium, anticonvulsants, antidepressants, beta-blockers and dopamine agonists, have been used to enhance the response to antipsychotic medications or to treat residual symptoms of chronic schizophrenia and comorbid conditions with schizophrenia (for reviews, see Miyamoto et al5, 8). However, despite the prevalence of the use of adjunctive therapies in clinical practice, there are very few empirical data and theoretical rationale to support this practice. The development of additional novel strategies to obtain potentially new antipsychotic compounds and their adjuncts possessing unique pharmacological profiles with few side effects is being pursued based on specific hypotheses, and actually more agents with antipsychotic efficacy are being developed. (for reviews, see Miyamoto et al5, 9). This article provides a brief review and critique of the current theory of mechanisms of action of antipsychotic drugs, and focuses on novel targets for therapeutic intervention and potential strategies for future drug development.

Current forms of treatment: first-generation antipsychotics and second-generation antipsychotics
The strategies and forms of treatment for schizophrenia vary according to the phase and severity of the illness. Pharmacologic treatment is the cornerstone and essential component of treatment for schizophrenia and its clinical management through the different stages of the illness. Although various psychosocial therapies, such as cognitive behavior therapy, psychoeducation and supported employment, are useful adjuncts to drug treatment,8, 10, 11 they all require pharmacologic treatment to be maximally effective. In particular, adequate pharmacotherapy during the acute stage of the illness could set the stage for subsequent long-term treatment. Although all available pharmacological treatments have limitations in their effectiveness and are associated with uncomfortable side effects, it is an established fact that antipsychotics can improve the psychotic symptoms of schizophrenia and prevent their recurrence.10, 11 At present, a total of 11 different classes of antipsychotic medications are available in the US. Among them are the currently available FGAs (phenothiazines, butyrophenones and thioxanthenes) which, although effective, are far from being optimal treatments. Between 30 and 60% of patients with acutely exacerbated psychotic symptoms either fail to respond to these drugs or respond inadequately or partially.12 In addition, they cause significant rates of undesirable acute and chronic adverse effects (for a review, see Miyamoto et al9). At this time, the only groups of patients in which the FGAs are clearly preferable are those for whom there is a clear indication for short- or long-acting injectable preparations (this will quickly change as injectable SGAs become more available), or who have a history of excellent response to a FGA with minimal side effects.13, 14 Prevailing Hypothesis For Schizophrenia Essay

Despite the superior clinical effectiveness and EPS profile of clozapine, its clinical utility is restricted by the propensity to cause agranulocytosis and mandatory hematological monitoring of patients. Newly developed SGAs in addition to the benzamide antipsychotic drugs (sulpirides and amisulprides) and aripiprazole, appear to provide important advances in side effect profile and efficacy for this drug class. However, a variety of side effects associated with individual SGAs and the substituted benzamides still affect patient health and quality of life in addition to their limitations in efficacy. Consequently, there is a continuing need for new and better drugs. Prevailing Hypothesis For Schizophrenia Essay